PUBLICATION
A new zebrafish model for experimental leukemia therapy
- Authors
- Mizgirev, I.V., and Revskoy, S.
- ID
- ZDB-PUB-100330-30
- Date
- 2010
- Source
- Cancer biology & therapy 9(11): 895-902 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Animals, Genetically Modified
- Antineoplastic Agents/pharmacology*
- Cell Line, Tumor
- Cyclophosphamide/pharmacology
- Dose-Response Relationship, Drug
- Green Fluorescent Proteins/genetics
- Green Fluorescent Proteins/metabolism
- Humans
- Larva/drug effects
- Larva/genetics
- Larva/metabolism
- Leukemia, Experimental/drug therapy*
- Leukemia, Experimental/pathology
- Microscopy, Fluorescence
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/pathology
- Prednisolone/pharmacology
- Survival Analysis
- Time Factors
- Vincristine/pharmacology
- Xenograft Model Antitumor Assays*
- Zebrafish/genetics
- Zebrafish/metabolism*
- PubMed
- 20339318 Full text @ Cancer Biol. Ther.
Citation
Mizgirev, I.V., and Revskoy, S. (2010) A new zebrafish model for experimental leukemia therapy. Cancer biology & therapy. 9(11):895-902.
Abstract
The efficacy of cyclophosphamide (CY), vincristine (VCR) and prednisolone (PRE) were studied in leukemia-bearing zebrafish larvae. A transplantable T cell acute lymphoblastic leukemia (T-ALL) line ZL1 was induced by mosaic expression of zRag2-EGFP-mMyc transgene and underwent more than 20 consecutive transplantations in adult syngeneic fish prior to the experiments. Drug efficiency was assessed by an increase of lifespan (ILS) of treated leukemia-bearing animals as compared with untreated leukemia-bearing animals. Different doses of the drugs and length of the treatment were tested. CY and VCR demonstrated therapeutic effect which was dose- and time course-dependent. The maximal increase of ILS reached 61.1% after CY (400 mg/L, 72 hours) treatment and 44.4%-in VCR (4 mg/L, 72 hours) treated animals. None of the tumor-bearing larvae showed complete recovery from leukemia as a result of any VCR and CY monotherapy schedule. PRE was inefficient for treatment of leukemia in zebrafish in a dose range between 1 and 50 mg/L and a treatment length between 24 and 72 hours due to it toxicity exclusively towards leukemia-bearing larvae. These data demonstrate that, in addition to morphological and genetic similarities with mammalian leukemia, zebrafish T-ALL is also sensitive to the same chemotherapeutic drugs in vivo as mammals. Therefore, this model can be utilized as a cost effective system for experimental tumor therapy and large-scale screening of anticancer compounds.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping